This is a continuing project with the long-term goal of identifying and characterizing components of the electroretinogram (ERG) which arise in the proximal retina. Particular attention is given to the studying the primate retina, in order to translate knowledge learned to human clinical patients. During past cycles of this work, we have identified the scotopic threshold response which arises from activity of the amacrine cells and is recorded under the very dark-adapted state; we also identified components from the ON- and OFF-neural pathways of the proximal retina that contribute to the light-adapted photopic ERG. We demonstrated that the a-wave near photopic threshold originates from hyperpolarizing second-order neurons and not directly from the cone photoreceptors. During the next period of work we will study the flicker ERG further, with the goal of developing a framework, possibly involving harmonic components, through which flicker analysis can be applied quantitatively to understand the waveforms found in human retinal dystrophies. We have devised a novel bioengineering approach to analysis of the ERG flicker response. By understanding what constitutes the normal components of the rapid-flicker response and by characterizing the altered response under known pharmacological conditions of blocking ON- or OFF-pathway neural activity, we will be able to provide qualitative and quantitative models of how ERG changes reflect mammalian, primate, and human retinal diseases. An overriding purpose in this work is to begin to apply ERG knowledge toward practical characterizing of the degree to which ERG changes correlate with retinal pathology in rodent models of retinal degeneration, in chemically-induced non-human primate retinopathy, and in the human condition by studying patients with hereditary progressive retinal degeneration.